I have been fortunate over my career to have a series of excellent mentors. Tom was an important mentor for me during my high school years. His enthusiasm and excitement for teaching, learning and research helped convince me that academic research was the right career path. He was a truly gifted educator that motivated many high school and college students. He will be greatly missed.

Thursday, September 18, 2008

What do biological networks reveal about epistasis and pleiotropy?

Our paper on "Shadows of complexity: What biological networks reveal and epistasis and pleiotropy" has been accepted for publication by BioEssays. Anna Tyler in my lab wrote much of this paper with help from myself, Dr. Folkert Asselbergs from Groningen and Dr. Scott Williams from Vanderbilt. The editor, Dr. Adam Wilkins, and the referees played a very important role in helping us shape this paper. One of the issues we addressed was how to define epistasis. The are classicial definitions from the early 1900s and more modern definitions based on what we know about systems biology. This paper builds on our previous paper on statistical vs. biological epistasis that was published in BioEssays in 2005. The link to information about the previous paper in PubMed can be found here. It was mentioned in a February 2005 post on this blog.

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene-gene interaction, has also been treated as an exception to the Mendelian one gene-one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of biomolecular networks. These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena.

MDR 2.0 alpha released

Version 2.0 alpha of our multifactor dimensionality reduction (MDR) software package has been released on Sourceforge.net. You can download it from here. More information about MDR can be found here. An MDR tutorial can be found in a 5-part series of posts on this blog from November to December of 2006.

This newest version of MDR includes a simple univariate estimation of distribution algorithm (EDA) that uses expert knowledge to probabilistically select SNPs from a genome-wide association study for MDR modeling. See my recent June 2008 post for more information.

This is an alpha version which means there might still be bugs or other problems despite our rigorous testing. Please keep this mind as you use it and email us feedback.

Thursday, September 04, 2008

2nd Annual Dartmouth Integrative Biology Symposium (April 29, 2009)

The 2nd Annual Dartmouth Integrative Biology Symposium will be held April 28 and 29 at Dartmouth College in Hanover, NH. There will be a student poster session and reception the evening of the 28th with the symposium all day on the 29th. The theme for the symposium will be "Emerging Technology". We are inviting speakers now and hope to have an agenda in the next month or two. Hold the date!

Also, I am thinking of organizing a 1/2 day MDR Workshop on the 28th. Email me if this is something you would seriously consider attending.

About Me

Edward Rose Professor of Informatics,
Director of the Institute for Biomedical Informatics, Director of the Division of Informatics in the Department of Biostatistics and Epidemiology,
Senior Associate Dean for Informatics,
The Perelman School of Medicine,
University of Pennsylvania